The biologic, functional and chemical characterization of human lymphoid cell surface antigens controlled by genes of the major histocompatibility complex (MHC) is under investigation. HLA typing of disease groups and families wherein several members are diseased has demonstrated a complex association of the MHC with the disease condition. Antigens not found in linkage disequilibrium in a normal population are found to mark psoriasis and psoriatic arthritis. Connective tissue diseases with overlapping clinical manifestations have distinct distribution of HLA alloantigens suggesting specific genetic contributions of the MHC to the disease state. Alloantisera detecting murine Ia antigens cross-react with human B lymphocyte and monocyte antigens (HLA-Dr). Human alloantisera detecting HLA-DRw antigens precipitate combinations of molecules of 4 different molecular weights. These antisera, when reacted with monocytes, induce specific T cell suppression of immunoglobulin synthesis and antigen stimulation. Monoclonal antibodies to lymphocyte cell surface antigens appear to identify functional subsets of T lymphocytes.